Immunotoxicology and allergy: Opportunities for in vitro analysis

The vertebrate immune system comprises a sophisticated network of organs, cells and molecules which must act in concert to provide host resistance to pathogenic micro-organisms and malignant disease. There is now compelling evidence that a variety of chemicals and drugs have the ability to depress one or more indices of immune function in rodents. In some cases it has been shown that such immune impairment is translated into a reduction in host resistance to experimental challenge with viruses, bacteria and/or transplantable tumours. However, the immune system clearly possesses a considerable functional reserve. The existence of compensatory and complementary mechanisms and the capacity of lymphoid tissue for renewal suggests that not all chemically-induced perturbations of immune function will necessarily compromise host resistance. Considerations of functional reserve, combined with the fact that xenobiotics may be able to influence immune function in many and varied ways, currently prohibits the development of reliable in vitro methods for the accurate identification of immunotoxins. The development of in vitro screens for assessing the potential of chemicals and drugs to induce allergy is similarly unrealistic at present. The induction of immune responses by chemical allergens requires a series of complex biological interactions which cannot yet be accurately modelled in vitro. Although purely in vitro methods for primary toxicological evaluation are not yet a possibility, an increasing appreciation of the important immunological events which provoke contact, respiratory and drug allergy is providing opportunities for the assessment of allergic potential using ex vivo techniques. Furthermore, in vitro techniques have played, and will continue to play, an important role in elucidating the cellular and molecular mechanisms through which drugs and chemicals may cause immunotoxicity.